Capillary-based analysis schemes, biochemical analysis, basic research in the biological sciences such as localized pH determinations in tissues and studies in protein folding, detection and study of microorganisms, and the miniaturization of instrumentation down to the size of a chip all require small volume detection. With the advent of lasers, light sources possessing unique properties including high spatial coherence, monochromaticity and high photon flux, unparalleled sensitivity and selectivity in chemical analysis has become possible; these technologies, however, can be both expensive and difficult to implement. In contrast, refractive index (RI) detection has been successfully applied to several small volume analytical separation schemes. For various reasons, RI detection represents an attractive alternative to fluorescence and absorbance: it is relatively simple, it can be used with a wide range of buffer systems, and it is universal, theoretically allowing detection of any solute, making it particularly applicable to solutes with poor absorption or fluorescence properties.
Further, recently developed methods utilizing refractive indices can require either the use of sequential measurements or the use of separate control measurements, such as in an adjacent capillary. The accuracy of such sequential or separate measurements can be less than ideal due to, for example, temperature changes that exist between measurements or between adjacent capillaries.
Accordingly, there is a need in the art for methods, systems, and apparatuses that can provide multiple refractive index related measurements simultaneously or substantially simultaneously without complications from, for example, thermal variations between sample and reference environments.